Methods for crimping a polymeric stent scaffold onto a delivery balloon

ABSTRACT

A medical device includes a polymer stent scaffold crimped to a catheter having an expansion balloon. A process for forming the medical device includes placing the scaffold on a support supported by an alignment carriage, and deionizing the scaffold to remove any static charge buildup on the scaffold before placing the scaffold within a crimper to reduce the scaffold&#39;s diameter. The polymer scaffold is heated to a temperature below the polymer&#39;s glass transition temperature to improve scaffold retention without adversely affecting the mechanical characteristics of the scaffold when deployed to support a body lumen.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to drug-eluting medical devices; moreparticularly, this invention relates to processes for crimping apolymeric stent to a delivery balloon.

2. Background of the Invention

The art recognizes a variety of factors that affect a polymeric stent'sability to retain its structural integrity when subjected to externalloadings, such as crimping and balloon expansion forces. Theseinteractions are complex and the mechanisms of action not fullyunderstand. According to the art, characteristics differentiating apolymeric, bio-absorbable stent scaffold of the type expanded to adeployed state by plastic deformation from a similarly functioning metalstent are many and significant. Indeed, several of the accepted analyticor empirical methods/models used to predict the behavior of metallicstents tend to be unreliable, if not inappropriate, as methods/modelsfor reliably and consistently predicting the highly non-linear behaviorof a polymeric load-bearing, or scaffold portion of a balloon-expandablestent. The models are not generally capable of providing an acceptabledegree of certainty required for purposes of implanting the stent withina body, or predicting/anticipating the empirical data.

Moreover, it is recognized that the state of the art in medicaldevice-related balloon fabrication, e.g., non-compliant balloons forstent deployment and/or angioplasty, provide only limited informationabout how a polymeric material might behave when used to support a lumenwithin a living being via plastic deformation of a network of ringsinterconnected by struts. In short, methods devised to improvemechanical features of an inflated, thin-walled balloon structure, mostanalogous to mechanical properties of a pre-loaded membrane when theballoon is inflated and supporting a lumen, simply provides little, ifany insight into the behavior of a deployed polymeric stent scaffold.One difference, for example, is the propensity for fracture or cracks todevelop in a stent scaffold. The art recognizes the mechanical problemas too different to provide helpful insights, therefore, despite ashared similarity in class of material. At best, the balloon fabricationart provides only general guidance for one seeking to improvecharacteristics of a balloon-expanded, bio-absorbable polymeric stent.

Polymer material considered for use as a polymeric stent scaffold, e.g.PLLA or PLGA, may be described, through comparison with a metallicmaterial used to form a stent scaffold, in some of the following ways. Asuitable polymer has a low strength to weight ratio, which means morematerial is needed to provide an equivalent mechanical property to thatof a metal. Therefore, struts must be made thicker and wider to have thestrength needed. The scaffold also tends to be brittle or have limitedfracture toughness. The anisotropic and rate-dependant inelasticproperties (i.e., strength/stiffness of the material varies dependingupon the rate at which the material is deformed) inherent in thematerial only compound this complexity in working with a polymer,particularly, bio-absorbable polymer such as PLLA or PLGA.

Processing steps performed on, and design changes made to a metal stentthat have not typically raised concerns for, or required carefulattention to unanticipated changes in the average mechanical propertiesof the material, therefore, may not also apply to a polymer stent due tothe non-linear and sometimes unpredictable nature of the mechanicalproperties of the polymer under a similar loading condition. It issometimes the case that one needs to undertake extensive validationbefore it even becomes possible to predict more generally whether aparticular condition is due to one factor or another—e.g., was a defectthe result of one or more steps of a fabrication process, or one or moresteps in a process that takes place after stent fabrication, e.g.,crimping? As a consequence, a change to a fabrication process,post-fabrication process or even relatively minor changes to a stentpattern design must, generally speaking, be investigated more thoroughlythan if a metallic material were used instead of the polymer. Itfollows, therefore, that when choosing among different polymeric stentdesigns for improvement thereof, there are far less inferences,theories, or systematic methods of discovery available, as a tool forsteering one clear of unproductive paths, and towards more productivepaths for improvement, than when making changes in a metal stent.

It is recognized, therefore, that, whereas inferences previouslyaccepted in the art for stent validation or feasibility when anisotropic and ductile metallic material was used, such inferences wouldbe inappropriate for a polymeric stent. A change in a polymeric stentpattern may affect not only the stiffness or lumen coverage of the stentin its deployed state supporting a lumen, but also the propensity forfractures to develop when the stent is crimped or being deployed. Thismeans that, in comparison to a metallic stent, there is generally noassumption that can be made as to whether a changed stent pattern maynot produce an adverse outcome, or require a significant change in aprocessing step (e.g., tube forming, laser cutting, crimping, etc.).Simply put, the highly favorable, inherent properties of a metal(generally invariant stress/strain properties with respect to the rateof deformation or the direction of loading, and the material's ductilenature), which simplify the stent fabrication process, allow forinferences to be more easily drawn between a changed stent patternand/or a processing step and the ability for the stent to be reliablymanufactured with the new pattern and without defects when implantedwithin a living being.

A change in the pattern of the struts and rings of a polymeric stentscaffold that is plastically deformed, both when crimped to, and whenlater deployed by a balloon, unfortunately, is not as easy to predict asa metal stent. Indeed, it is recognized that unexpected problems mayarise in polymer stent fabrication steps as a result of a changedpattern that would not have necessitated any changes if the pattern wasinstead formed from a metal tube. In contrast to changes in a metallicstent pattern, a change in polymer stent pattern may necessitate othermodifications in fabrication steps or post-fabrication processing, suchas crimping and sterilization.

One problem encountered with a polymer stent is the stentssusceptibility to damage when being crimped to a balloon. Non-uniformforces applied during a crimping process can cause irregulardeformations in struts of a polymer stent, which can induce crackformation and loss of strength. There is a continuing need to improveupon the crimping methods, or pre-crimping procedures used for polymerstents to reduce instance of crack formation or irregular strutdeformation during stent production.

SUMMARY OF THE INVENTION

The invention provides a process for crimping a polymer stent scaffold,or scaffold to a balloon. The polymer scaffold is expanded for placementwithin a lumen of the body by plastic deformation of the polymerscaffold of the scaffold. The crimping process used to place thescaffold on the balloon includes, in one embodiment, a pre-crimp andfinal crimp step.

It was discovered that polymer scaffolds are susceptible to damage ifthey have a slight misalignment with jaws of a crimper. A “slight”misalignment means a misalignment that the art has tolerated in the pastand has assumed were present but not capable of significantly effectinghow the scaffold would be deformed by the crimper as compared to thesame scaffold when perfectly aligned with jaws of the crimper. Suchmisalignment tolerance will be understood by reference to informationavailable from a manufacturer of a commercially available crimpingdevice. The inventor discovered, unexpectedly, that if a “slight”misalignment is removed, or substantially removed, when crimping apolymer scaffold, there is a significant reduction in the irregulardeformations of scaffold struts that are sufficient to cause irreparabledamage to a polymer scaffold, e.g., a PLLA scaffold.

According to the invention, one or more improvements in alignment for apolymer scaffold are included in the crimping process as in, accordingto one embodiment, a pre-crimp process. Preparation for the pre-crimpprocess includes a deionizing step to remove static buildup on thepolymer scaffold. By removing a static charge on the polymer material,the scaffold should sit more level on the support, i.e., a rod, mandrelor catheter, thereby improving alignment with the crimper. Additionalmeasure may be employed. A carriage support for positioning the scaffoldwithin the crimper includes a magnetic element for engagement with anend of the support holding the scaffold. The scaffold support is held toa surface of the base e.g., a grooved channel proximal to, or formed bythe magnetic element, by a magnet force of attraction. When the surfaceof the base is aligned with the crimper, so too will the support alignwith the crimper. Less operator skill is required to align the scaffold.Slight misalignments causing damage when the polymer scaffold is crimpedare, therefore, more often avoided. Existing devices for scaffoldalignment, by contrast, use mechanical devices, e.g. lock knobs, thatrequire adjustment, which can lead to more frequent misalignmentproblems.

A first and second carriage support may be used to support both ends, asopposed to only one end of the scaffold support. In this alternativeembodiment, the two ends of the scaffold support are supported bycontacting surfaces of the respective bases of the carriage supports andheld thereto by a magnet force of attraction. Each base support islocated on opposite ends of the crimper. Alternatively, only one of thebases may employ a magnet. The second base is provided so that the freeend of the scaffold support may be supported in addition to the fixedend to provide better accuracy in alignment. The second base may providea flat surface level with the surface of the first base support surface,or each may have grooves to receive the ends of the scaffold support, inprecise alignment with the central axis of the crimper. This arrangementmay further reduce requirements for operator skill when aligning thestent with the crimper, e.g., the operator need only place the ends ofthe scaffold support within the aligned grooves.

Supporting both ends of the scaffold also permits it to support moreweight without deflecting, which causes misalignment. A scaffoldsupport, supported by two movable rails preferably as fixed (i.e., 6degree of freedom restraint at both ends), may also be used to perform apre-crimping process for two stents. A first and second carriage, whichmove left to right or right to left along rails in unison, each supporta scaffold on opposite sides of the crimper. In this arrangement a stenton one side of the crimper may be pre-crimped first, followed by thestent on the opposite side. Alternatively, stents may be disposed on theimproved support so that two or more scaffolds may be crimpedsimultaneously. This increases production efficiency for a pre-crimp.

After being more suitably aligned, the polymer scaffold may be insertedinto the crimper to reduce its diameter to a pre-crimp diameter. Thereduced-diameter scaffold is then removed from the scaffold support,placed on, and aligned with the balloon of the delivery catheter. Thescaffold is then crimped to a final crimped diameter on the balloon.Preferably, a multi-step final crimping process includes heating thescaffold to a temperature just below the glass transition temperature ofthe polymer to avoid damaging the scaffold when it is crimped andwithout significantly altering the scaffold's deployedstrength/stiffness characteristics.

In one aspect of the invention there is a method for crimping aballoon-expanded stent scaffold to a balloon, comprising the steps ofproviding a tube; radially expanding the tube to increase its radialstrength; forming the scaffold from the radially-expanded tube,including the steps of forming a circumferential series of closed cellshaving a W-shape and linear link struts connecting the W-shape cells.The scaffold is deionized and then the deionized scaffold is crimped tothe balloon. Preferably the scaffold is deionized just prior to beinginserted into the crimper to avoid damage to the scaffold when crimped.

In another aspect, there is a method for crimping a balloon-expandedpolymer scaffold to a balloon using a crimper, comprising the steps of:performing a pre-crimp of the polymer scaffold to reduce the diameter ofthe scaffold before crimping the scaffold to the balloon. The pre-crimpsteps include aligning a support with jaws of the crimper by affixing afirst end of the support to a carriage having a surface adapted forsupporting the first end of the support to the carriage by a magneticforce, disposing the polymer scaffold on a second end of the support,and deionizing the polymer scaffold. The deionized polymer scaffold isthen placed in the crimper while supported on the support, and itsdiameter reduced. After this diameter reduction, the scaffold is crimpedto the balloon.

In another aspect, there is a crimping system for a scaffold, includinga crimper, a scaffold support having first and second ends, the scaffoldbeing supported on the scaffold support, a first base support forsupporting the first end, a second base support having a second end,wherein the first and second base supports are disposed on oppositesides of the crimper. Both base supports may have a magnet for holdingthe scaffold support ends.

The scope of the methods and apparatus of the invention also encompassprocesses that crimp a scaffold as substantially described in US Pub.No. 2010/0004735 and US Pub. No. 2008/0275537. The thickness of the tubefrom which the scaffold is formed may have a thickness of between 0.10mm and 0.18 mm, and more narrowly at or about 0.152 mm. The scaffold maybe made from PLLA. And the scaffold may be crimped to a PEBAX balloon.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference, and as if eachsaid individual publication or patent application was fully set forth,including any figures, herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a process for fabricating a scaffold of a polymer scaffoldand crimping the fabricated scaffold to a balloon according to theinvention.

FIG. 2 is planar view of a portion of a polymer scaffold that wascrimped to a balloon according to aspects of the invention. This viewdescribes the scaffold pattern of the load-bearing structure of thescaffold of the fully deployed scaffold that is crimped to a balloonaccording to the process of FIG. 1.

FIG. 3 is a schematic view showing a first embodiment of a scaffoldalignment apparatus and method.

FIG. 4 is a schematic view showing a second embodiment of a scaffoldalignment apparatus and method,

FIG. 5 is a schematic view showing a third embodiment of a scaffoldalignment apparatus and method.

DETAILED DESCRIPTION OF EMBODIMENTS

The invention arose out of a need to solve a problem of high rejectionrates, for polymer scaffolds during a pre-crimp process that could notbe explained, or cured by existing methods for diagnosing or solving,respectively, crimping problems. During a pre-crimp process, thescaffold diameter is reduced to a diameter intermediate of its startingdiameter and a final crimped diameter on the balloon. After thescaffold's diameter has been reduced in diameter by the crimper, thescaffold is placed on a balloon of the delivery catheter and re-insertedinto the crimper. The crimper reduces the scaffold diameter to itsfinal, crimped diameter on the balloon. When reduced down to the finalcrimped diameter, there is a retention force between the scaffold andballoon for retaining the scaffold on the balloon. The disclosure refersto a stent “scaffold”. It will be understood that the same processes andapparatus described herein apply to a balloon expandable “stent” thatuses a scaffold as its load bearing structure.

For the pre-crimp phase of the process the scaffold is supported on adistal end of a scaffold support, such as a rod, mandrel or catheter.The proximal end of the scaffold support is held on a base support,which is relied on to align the scaffold support distal end, where thescaffold is located, with the jaws of the crimper so that the scaffoldmay be properly positioned within the crimper before it is deformed toits pre-crimp diameter. This process is carried out in an environmentthat is relatively sterile and having low humidity. As will beappreciated, when the scaffold is within the crimper and the crimpingforce applied, the interaction between surfaces of the scaffold and thecrimper jaws as the scaffold is being deformed to a reduced diametercannot be visually inspected. The scaffold's scaffold is being deformedwithin a cavity that completely blocks the scaffold from view. As such,an operator cannot identify irregular deformations of the scaffold as itis being deformed. A scaffold that, when deformed, develops irregularlybent, or twisted struts cannot be discovered until after it is removedfrom the crimper and visually inspected. At this point, irreparabledamage has occurred and the scaffold is discarded.

As is generally known in the art, the nature of deformation of anarticle through externally applied forces may, in some situations, beinferred from the reaction forces applied by the article against thebody, through which the external force is applied. For example, if thebody applying the force to the article is programmed to enforce adisplacement at a prescribed rate, monitoring the changes in the forceneeded to maintain the enforced displacement can give clues as to howthe body is being deformed. In the case of a scaffold, an operator canset the rate for crimping and monitor the applied force. However, theknown methods for instrumentation are not capable of providing the levelof accuracy needed to infer how individual struts are being deformed bycrimper jaws. The operator, therefore, has virtually knowledge about howthe scaffold's struts are being deformed within the crimper. The onlyknowledge that the operator has about how the scaffold might have beendeformed when in the crimper occurs when the scaffold is withdrawn fromthe crimper and visually inspected. Again, at this point irreparabledamage has occurred and the scaffold is discarded.

The inventor was presented with the problem of a high proportion ofpolymer scaffolds being rejected because struts of the scaffold werebeing irregularly deformed during a pre-crimp process, and suchirregularly deforming damage would potentially cause the fractures orbroken struts during polymeric stent deployment. Scaffold strength andstiffness concerns raised by the appearance of irregular deformations ata pre-crimp stage are only compounded if the scaffold is then deformedfurther during a final crimping to the balloon. As will be appreciated,irregular deformations of scaffold struts can often occur. When strutsof a polymer scaffold are irregularly bent or twisted, however, they aremore often deemed unacceptable than if this were to occur the scaffoldwas formed from a metal. Irregular bending or twisting of polymer strutscan lead to cracks and fracture, an uncommon occurrence in metalscaffolds. Thus, acceptable irregularities for a crimped metal scaffoldare, in many cases, unacceptable for a polymer scaffold.

The solution to the problem of high rejection rates faced by theinventor was quite elusive, for two reasons. First, because there was noavailable means for tracking the deformation of the polymer scaffoldwithin the crimper, it was not known whether the problem was due to thecrimper, a process occurring during fabrication of the scaffold, or thealignment of the scaffold in the crimper. Despite extensive knowledge inthe art concerning crimping, no previously proposed crimping-relatedprocess known to the inventor, or methods for diagnosing a crimpingproblem shed any light on a solution to the problem. Second, the art hasdealt rather extensively with improving crimping processes for metalscaffolds. However, the assumptions made about the scaffold whenimproving crimper processes, or problem-solving, have ignored, orunderestimated significant differences between polymer and metalscaffolds. First, irregular deformations of metal scaffold struts, whilenot desirable, are often acceptable. The same is not true of a polymerscaffold due to its material properties. Second, polymer scaffolds aremore susceptible to irregular deformations than metal scaffolds due tothe reduced space between polymer struts vs. metal struts (polymerstruts are thicker than metal struts having equivalent stiffnessproperties). The existing art pertaining to crimpers fails to adequatelyaccount for these differences.

It was discovered that electrostatic charges that can develop on apolymer scaffold was a key cause for scaffold damage. The influence ofthis charge was noticed when the scaffold, supported on the scaffoldsupport, was visually inspected. One end of the scaffold was raisedslightly higher off the scaffold support than the opposite end. Whenpressure was applied to the raised end of the scaffold, e.g., byapplying finger pressure, then this pressure was released, the endreturned to its raised position. When the scaffold was sprayed by ade-ionizing spray, the upwards bias of the scaffold end disappeared. Itwas concluded, therefore, that the raised end was caused by anelectro-static charge on the scaffold.

The ability of material to surrender its electrons or absorb excesselectrons is a function of the conductivity of the material. Forexample, a pure conductor, such as copper, has a rigid molecularconstruction that will not permit its electrons to be moved aboutfreely. Non-conductive materials, such as a polymer, e.g., PLLA, have amolecular construction that is more easily disrupted by friction, heator pressure applied to the material to induce a charge on the surface.If the conductivity of the surface is controlled, then a static chargecan be avoided. Adding surface conductivity to the polymer can preventthe buildup of static electricity. This is normally accomplished by useof additives such as moisture and anti-static sprays. Typicalanti-static sprays are made from a soap based material diluted in avolatile solvent. The solvent evaporates leaving a conductive coating onthe surface of the material. The polymer surface becomes conductive. Aslong as the coating is not disturbed, a static charge can be avoided.Electric deionizers, known in the art, may also be used.

Scaffolds designated for pre-crimping were deionized by an electricdeionizer before pre-crimping, to determine whether the removal of astatic charge would have an effect on how the scaffold was crimped. Whenthe deionized scaffolds were removed from the crimper, there were fewerinstances of irregular deformations in the struts. Based on thisdiscovery, it was thought that electro-static charges, which caused thescaffold to misalign with the crimper, induced non-uniform resistance todeformation within the crimper to cause struts to bend and twistirregularly when being crimped. The presence of a static charge andresulting misalignment of a scaffold that might occur due to thepresence of this charge was not surprising (the scaffold is made from apolymer). However, the effect on crimping due to the presence of thischarge and resulting misalignment was quite surprising. A relativelyminor change to the crimping process, i.e., deionizing the scaffold justprior to crimping, was disproportionate to the change in resultsproduced.

About 600 scaffolds were evaluated using a pre-crimping process thatincluded a deionization step. With this step included in thepre-crimping process the rejection rate was reduced from 60% to lessthan 30% (about 26%)—a dramatic improvement.

To achieve similar results, the scaffolds may be sprayed or immersed ina deionization solution, or an electric deionizer may be used, beforebeing fitted onto a support. The scaffold support 20, e.g. surfaces ofthe balloon, and/or scaffold may be sprayed just prior to inserting thescaffold into the crimping device. Further, following any adjustment ofthe scaffold on the support the scaffold may be sprayed again by adeionization solution since any sliding motion between the surfaces mayagain cause a static charge buildup. According to one embodiment apre-crimp process for a deionized scaffold is followed by a final crimpprocess that includes a second deionization step just after finalalignment. After the scaffold has been aligned with balloon markers thescaffold and balloon are deionized by an electric deionizer to removeany possible static buildup between the surfaces that occurred duringfinal alignment.

Based on the foregoing, it was hypothesized that other refinements tothe alignment of a polymer scaffold within a crimper might furtherreduce rejection rates. In addition to deionizing the polymer scaffoldwhen it sits on the scaffold support, e.g., rod, mandrel or catheter,the base that holds the scaffold support in place was modified to enablemore precise alignment with the crimper. As it turns out, betteralignment of the scaffold support position relative to the crimper alsoimproved results. From this finding, it was confirmed that, in general,a misaligned polymer scaffold is more susceptible to damage within acrimper than a corresponding misaligned metal stent. A polymer scaffoldthat has a “slight” misalignment within the crimper has a far greaterchance of becoming damaged.

The known art provides apparatus for aligning and supporting a scaffoldon a scaffold support when it is placed between the jaws of a crimper.Such commercial crimping systems are well known. One such crimpingsystem provides a base support having a gripper or jaws for holding oneend of the scaffold support to the base. For example, a lock knob isused to tighten-down the scaffold support to hold it in place. Ascaffold is then placed on the end of the scaffold support, or thescaffold is placed on the scaffold support before the scaffold supportis secured to the base. The supported scaffold is then inserted into thecrimper by moving the end of the scaffold support into the jaws of thecrimper. The engagement of the crimper jaws on the scaffold using thisarrangement has proved satisfactory in the past. But when faced with theunexplained number of rejected scaffolds crimped using this crimpingsystem and the discovery that more precise alignment is needed for apolymer scaffold during crimping, it was suspected that an improvementin alignment might yield still better results for a pre-crimp process,in addition to deionizing the scaffold before crimping.

A base that uses a lock knob, or mechanical lock is susceptible tocreating conditions where the scaffold support is not sufficientlyaligned with the crimper. For example, if the knob is tightened down toomuch, or not enough, the scaffold support can be orientated slightly upor down. This arrangement can frequently produce a slight misalignmentof the scaffold with the crimper jaws, which can result in an irregulardeformation during diameter reduction. The degree of this misalignmentby an operator, for example, when performing routine scaffold alignmentfor a pre-crimp, was previously thought slight and not of significanceto suspect that an improvement in scaffold alignment was necessary.However, the inventor's discovery concerning alignment within a crimperfor a polymer scaffold, as opposed to a metal scaffold, revealed thatprecise alignment was more important than previously thought.

FIG. 3 shows an alignment carriage for a polymer scaffold. The alignmentcarriage includes carriage 40 include an alignment surface 40 a and amagnetic element 50 disposed on or near the surface 40 a. The carriageis movable towards/away from a crimping device 30. The axis of alignmentis depicted as axis A. The scaffold 10, e.g., scaffold with a stentpattern 200 or intermediate pattern 216 (described below) is supportedon a support 20, which is held along axis A by carriage 40.

The carriage 40 is moved towards and away from the crimping device 30,e.g., an iris crimper having a crimper head portion 30 a and jaws 32,along a rail 45 in such a manner that support 20 remains parallel withaxis A and the central axis of the crimping device 30. When alignment isachieved, all exterior surfaces, proximal and distal, of the scaffold 10receive the jaws 32 at about the same time. To achieve this condition,the scaffold 10 is disposed within the head 30 a and equidistant betweenjaws 32 so that there is a near perfect, uniform radial compression ofthe scaffold to avoid irregular twisting or bending of scaffold struts.Alignment of surface 40 a with axis A, so that when support 20 is flushwith surface 40 a its central axis lies on axis A and extends parallelthereto, may be accomplished using a well-known laser alignment systemor other suitable device. The support 20, when placed on surface 40 a issecurely held thereto by a magnetic force of attraction between element50 and a metal portion of the support 20. The support 20 need only belaid flush with the surface 40 a. A groove formed on surface 40 a andextending parallel to axis A may be used to assist with aligning support20 properly on surface. There is no mechanical adjustment needed to holdthe support 20 to the base 40. As such, there is less tendency for ascaffold support to become misaligned relative to axis A by an operator.

An anti-static air-gun or nozzle 52 is directed towards the crimperheads and scaffold 10 to remove any static charge existing on thepolymer scaffold 10 and/or in the crimper during the pre-crimp. The airgun may be passed over the scaffold before it is inserted into thecrimper. Or the air gun may be disposed adjacent the opening (as shown)and run during the pre-crimp. The carriage 40 travels along the rail 45to place the end of the support 20 and scaffold 10 within the head 30 a,and then remove the scaffold 10 and support 20 from the head 30 a afterpre-crimp.

In an alternative embodiment, a second base support 41 may be providedat the opposite side of the crimper 30 to support end 20 b of thescaffold support 20, as depicted in FIG. 4. This arrangement supportsthe scaffold support at both ends 20 b, 20 a as opposed to thecantilever-type support depicted in FIG. 3. The first base support 40 aslocated on one side of the crimper 30 and the second base support 41 islocated at the opposite side of the crimper 30. Each may be controlledby the same rail mechanism, which moves the bases 40/41 together fromside to side. Second base support 41 may be constructed as part of analignment carriage like the alignment carriage described in connectionwith FIG. 3. Thus, base support 41 may be part of an alignment carriagemovable along a rail 45 and including a surface (not shown) to receivethe end 20 b on a flat or grooved surface. A magnet may also be disposedon or near this surface to hold the end 20 b of the scaffold support 20in place. When aligning scaffold support 20 and scaffold 10 the surfacesare brought together to support scaffold support 20 at ends 20 a, 20 b.Then both bases 40, 41 are moved right to left in FIG. 4 to place thealigned scaffold 10 within the crimper 30. Referring to FIG. 4,alternatively, second base 41 may have a clamp with an upper bearingsurface portion 41 a and lower bearing surface 41 b. A knob or screw 43is used to bring the two surfaces 41 a, 41 b together to grip the end 20b. An anti-static air gun 52 is used to remove static charge. The lengthof surface 40 a and magnet strength and corresponding length of surface40 a on the left side (if a clamp is not used) is such that both supportends 20 a, 20 b are restrained in a fixed-type arrangement (i.e., theyare not pinned at the ends). Thus, the end 20 a and end 20 b cannotrotate about any axis because it is fixed. This arrangement facilitatesthe degree of precision the inventor found is sometimes needed toimprove polymer scaffold crimping.

In either of the embodiments described in connection with FIG. 4, or inconnection with FIG. 5, the base supports 40, 41 may be operated toapply a tension force to the scaffold support 20 (by moving the bases40, 41 slightly apart). By applying a tension T, one can remove anypossible sagging of the scaffold support 20, as may be necessary due toan extended length of the scaffold support 20 needed to support bothends 20 a, 20 b on opposite sides of the crimper 20. Additionally, withregards to the embodiments described in relation to FIG. 4 andembodiments associated with FIG. 5, more than the stents illustrated maybe disposed on the support 20 due to the fixed support (as opposed tocantilever at one end). Since the support 20 is supported at both endsthe support 20 should not deflect in the middle due to the weight of thescaffolds, or its own weight. A tension T may also be applied if neededto maintain precise alignment with the crimper axis. Thus, in theembodiment depicted in FIG. 4 two scaffolds may be crimped at the sametime.

FIG. 5 shows another embodiment of a scaffold alignment system. Twobases 40, 41 are disposed on opposite sides of the crimper 30. Each baseincludes a magnet 50 for retaining the ends 20 a, 20 b to the bases 40,41 respectively. The alignment is achieved by placing the ends 20 a, 20b on the bases 40, 41 as before in FIG. 3. In this embodiment, a firstand second scaffold 10 is located on opposite sides of the crimper 30 sothat both scaffolds may be crimped, one after another. The scaffold 10on the right in FIG. 5 is moved into the crimper 30 by displacing thebases 40, 41 along rails 45, 46 from right to left. The air gun 52 isused to remove static charge. After this pre-crimp is complete, thescaffold 10 on the left of the scaffold is pre-crimped by moving thebases 40, 41 from left to right. A second or the same anti-static airgun 52 is used to remove a static charge. A tension T may be applied tosupport 20 as in the embodiment depicted in FIG. 4.

According to the disclosure, a scaffold fabrication, pre-crimping andfinal crimping process including the alignment steps just described isalso provided. The scaffold fabrication process includes forming thescaffold from an expanded tube to increase its strength and stiffnesscharacteristics. The crimping process is, preferably, multi-step andincludes a selection of a narrow temperature range for heating thescaffold, selected according to the glass transition temperature for thepolymer.

A “glass transition temperature,” Tg, is the temperature at which theamorphous domains of a polymer generally change from a brittle, vitreousstate to a solid deformable or ductile state at atmospheric pressure. Inother words, the Tg corresponds to the temperature where the onset ofnoticeable segmental motion in the chains of the polymer occurs. When anamorphous or semi-crystalline polymer is exposed to an increasingtemperature, the coefficient of expansion and the heat capacity of thepolymer both increase as the temperature is raised, indicating increasedmolecular motion. As the temperature is raised the actual molecularvolume in the sample remains constant, and so a higher coefficient ofexpansion points to an increase in free volume associated with thesystem and therefore increased freedom for the molecules to move. Theincreasing heat capacity corresponds to an increase in heat dissipationthrough movement. Tg of a given polymer can be dependent on the heatingrate and can be influenced by the thermal history of the polymer.Furthermore, the chemical structure of the polymer heavily influencesthe glass transition by affecting mobility.

Poly(L-lactide) (PLLA) and Poly(lactide-co-glycolide) (PLGA) areexamples of a class of semi-crystalline polymers that may be used toform the scaffold structure described herein. PLLA is a homo-pomonomer,while PLGA is a co-polymer. The percentage of Glycolic Acid (GA) in ascaffold constructed of PLGA may be between 0-15%. For PLLA, the onsetof glass transition occurs at about 55° C. For PLGA, an increase of GAfrom about 0% to 15% lower range for Tg to about 50° C.

In one embodiment, a tube is formed by an extrusion of PLLA. The tubeforming process described in US Pub. No. 2010/00025894 may be used toform this tube. The finished, solidified polymeric tube of PLLA may thenbe deformed in radial and axial directions by a blow molding processwherein deformation occurs progressively at a predetermined longitudinalspeed along the longitudinal axis of the tube. For example, blow moldingcan be performed as described in U.S. Publication No. 2009/0001633. Thisbiaxial deformation, after the tube is formed, can produce noticeableimprovement in the mechanical properties of the scaffold structuralmembers cut from the tube without this expansion. The degree of radialexpansion that the polymer tube undergoes characterizes the degree ofinduced circumferential molecular or crystal orientation. In a preferredembodiment, the radial expansion ratio or RE ratio is about 400% of thestarting inner tube diameter and the axial expansion ratio or AE ratiois about 150% of the starting tube length.

The above scaffold's outer diameter may be designated by where it isexpected to be used, e.g., a specific location or area in the body. Theouter diameter, however, is usually only an approximation of what willbe needed during the procedure. For instance, there may be extensivecalcification that breaks down once a therapeutic agent takes effect,which can cause the scaffold to dislodge in the vessel. Further, since avessel wall cannot be assumed as circular in cross-section, and itsactual size only an approximation, a physician can choose to over-extendthe scaffold to ensure it stays in place. For this reason, it ispreferred to use a tube with a diameter larger than the expecteddeployed diameter of the scaffold.

In one embodiment the ratio of deployed to fully crimped diameter isabout 2.5. In this embodiment, the crimped diameter corresponds to anouter diameter that is only about 40% of the starting diameter. Hence,when deployed the drug eluting scaffold is expected to increase in sizeup to about 2.5 times its stowed or crimped diameter size.

In one particular example, a scaffold is formed from a biaxiallyexpanded tube having an outer diameter of 3.5 mm, which approximatelycorresponds to a deployed diameter (the scaffold may be safely expandedup to 4.0 mm within a lumen). When crimped on the balloon, the scaffoldhas an outer diameter of 1.3 mm, or about 37% of the starting tubediameter of 3.5 mm.

As discussed earlier, fabrication of a balloon-expanded polymer scaffoldpresents challenges that are not present in metallic scaffolds. Onechallenge, in particular, is the fabrication of a polymer scaffold,which means the load bearing network of struts including connectorslinking ring elements or members that provide the radial strength andstiffness needed to support a lumen. In particular, there exists anongoing challenge in fabricating a polymer scaffold capable ofundergoing a significant degree of plastic deformation without loss ofstrength. In the disclosed embodiments, a polymer scaffold is capable ofbeing deformed from a crimped diameter to at least 2.5 times the crimpeddiameter without significant loss of strength. Moreover, the polymerscaffold is retained on a delivery balloon with a retention force thatis significantly higher than previous methods of scaffold retention fora polymer scaffold.

There is a certain degree of beneficial movement between interconnectedpolymer chains of a scaffold structure heated to temperatures just belowTg of the polymer when the scaffold is being crimped to a balloon,versus the same scaffold crimped to the balloon at a lower temperature,such as room temperature. For example, for a controlled temperature ofbetween about 48° C. and 54° C., 48-50° C. or 48° C. it was found that aPLLA scaffold crimped to a balloon exhibited noticeable improvement inthe retention force of the scaffold on the balloon, while notconcomitantly producing unacceptable side effects for the deployedscaffold, e.g., excessive cracking, void formation, fracture and/or lossof memory in the material affecting its deployed radial strengthqualities.

One problem encountered with fabrication of a scaffold for delivery to asite in a body using a balloon is the ability of the scaffold to besafely crimped to the balloon so that an adequate retention force isestablished between the scaffold and balloon. A “retention force” for ascaffold crimped to a balloon means the maximum force, applied to thescaffold along the direction of travel through a vessel, which thescaffold-balloon is able to resist before dislodging the scaffold fromthe balloon. The retention force for a scaffold on a balloon is set by acrimping process, whereby the scaffold is plastically deformed onto theballoon surface to form a fit that resist dislodgment of the scaffoldfrom the scaffold. Factors affecting the retention of a scaffold on aballoon are many. They include the extent of surface-to-surface contactbetween the balloon and scaffold, the coefficient of friction of theballoon and scaffold surfaces, and the degree of protrusion or extensionof balloon material between struts of the scaffold. For a metal scaffoldthere are a wide variety of methods known for improving the retentionforce of a scaffold on a balloon via modification of one or more of theforegoing properties; however, many are not suitable or of limitedusefulness for a polymeric scaffold, due to differences in mechanicalcharacteristics of a polymer scaffold verses a metal scaffold asdiscussed earlier. Most notable among these differences is brittlenessof the polymer material suitable for balloon-expanded scaffoldfabrication, verses that of a metal scaffold. Whereas a metal scaffoldmay be deformed sufficiently to obtain a desired retention force, therange of deformation available to a polymer scaffold, while avoidingcracking or fracture-related problems, by comparison, is quite limited.

For polymeric scaffolds, the glass transition temperature (Tg) of itsmatrix material has to be higher than physiological temperatures (37°C.) in order to maintain radial strength after implantation. A scaffoldformed from PLLA has a Tg of about 55-60° C. When a PLLA scaffold iscrimped to a balloon at around 25° C., a free polymer chain movementhardly occurs. As a consequence, the PLLA is brittle and susceptible tocrack formation. Moreover, at this temperature, well below Tg, thescaffold will tend to recoil or revert towards its starting diameter ofthe tube, to a certain degree, due to the memory in the material. Inother others, when the scaffold is deformed during crimping, the inducedstrain in the polymer matrix will cause the scaffold to enlarge to acertain degree once the crimping force is removed, since there will besome percentage of elastic deformation when the scaffold is crimped tothe balloon, which causes the scaffold to revert towards its originaldiameter when the crimping force relieved. This degree of elasticrecoil, so to speak, limits the amount of retention of the scaffold onthe balloon since the degree of contact between scaffold and balloon isreduced. Stated somewhat differently, when there is elastic recoil to alarger diameter, the normal force the scaffold imparts on the balloonwhile the crimping force is applied, which is proportional to magnitudeof the retention force, decreases once the crimper is removed due to thepercentage of elastic recoil in the scaffold.

FIG. 1 is a process diagram illustrating the steps used to fabricate apolymer scaffold and crimp the scaffold to a balloon. In this example, ascaffold was formed from a radially expanded tube of PLLA. The scaffoldhad a strut pattern as shown in FIG. 2. The struts had a thickness ofabout 0.152 mm and the balloon used was a PEBAX balloon. An iris crimperwas used to pre-crimp and final crimp of the scaffold to the balloon.

A crimping process may proceed as follows. In preparation for apre-crimp scaffold, the scaffold is deionized and aligned with thecrimper 30 using the alignment system of FIG. 3. Then, the crimp headdiameter is moved to an intermediate position that is larger than thescaffold starting outer diameter (OD). The temperature of the jaws israised to, or to about 48° C. and is allowed to stabilize at thattemperature. The scaffold is pre-crimped then removed from the crimper.

In the embodiments, an anti-static filtered air gun is used to deionizethe scaffold before and/or during pre-crimping. Before pre-crimp, theanti-static air gun is passed over the scaffold front to back to removestatic charges on the scaffold. In one case, the anti-static filteredair gun is applied for 10 seconds to 1 minute along the scaffold. Inanother embodiment, the air gun deionizes the scaffold duringpre-crimping. The anti-static filtered air gun is applied for 10 secondsto 1 minute along the scaffold.

A delivery catheter (holding the balloon) is chosen with the correctsize to fit the scaffold. The scaffold is placed onto the balloon of thecatheter with the distal portion of the scaffold aligned with the distalportion of the catheter. The catheter is then placed onto the slidingalignment carriage 40. A final adjustment is made to the scaffold toposition it between balloon markers on the catheter. The scaffold andcatheter is moved into the crimp jaws, by sliding the carriage 40forward along the rail 45.

The cycle is initiated by the operator. As an example, for a 3.0×18 mmscaffold, the ID of the crimp head moves to a diameter of 0.083″ whereit remains for 30 seconds. This is stage 1. The system movesautomatically to stage 2 where the head moves to an ID of 0.068″ and isheld for 15 seconds. During this stage, the balloon catheter is inflatedto 17 psi. After this stage is complete, the balloon is deflated and thecrimp head is opened to allow the catheter to be removed. The scaffoldreceives a final alignment to the balloon markers. The scaffold andballoon are placed back into the crimp head. The operator initiatesstage 3 where the head is reduced to 0.070″ diameter for 10 seconds.During this stage 3, the balloon is also inflated to 17 psi. Oncecomplete, the machine moves automatically to the stage 4, where theballoon is deflated and the crimp head ID is reduced to 0.047″ and isheld for 200 seconds. When this fourth and final stage is complete, thehead opens and the catheter and scaffold removed. The scaffold isretained on the balloon and is immediately placed into a sheath.

As noted above, in a preferred embodiment a scaffold has the scaffoldpattern described in U.S. application Ser. No. 12/447,758 (US2010/0004735) to Yang & Jow, et al. Other examples of scaffold patternssuitable for PLLA are found in US 2008/0275537.

FIG. 2 shows a detailed view of an intermediate portion 216 of a strutpattern 200 depicted in US 2010/0004735. The intermediate portionincludes rings 212 with linear ring struts 230 and curved hinge elements232. The ring struts 230 are connected to each other by hinge elements232. The hinge elements 232 are adapted to flex, which allows the rings212 to move from a non-deformed configuration to a deformedconfiguration. Line B-B lies on a reference plane perpendicular to thecentral axis 224 depicted in US 2010/0004735. When the rings 212 are inthe non-deformed configuration, each ring strut 230 is oriented at anon-zero angle X relative to the reference plane. The non-zero angle Xis between 20 degrees and 30 degrees, and more narrowly at or about 25degrees. Also, the ring struts 230 are oriented at an interior angle Yrelative to each other prior to crimping. The interior angle Y isbetween 120 degrees and 130 degrees, and more narrowly at or about 125degrees. In combination with other factors such as radial expansion,having the interior angle be at least 120 degrees results in high hoopstrength when the scaffold is deployed. Having the interior angle beless than 180 degrees allows the scaffold to be crimped while minimizingdamage to the scaffold struts during crimping, and may also allow forexpansion of the scaffold to a deployed diameter that is greater thanits initial diameter prior to crimping. Link struts 234 connect therings 212. The link struts 234 are oriented parallel or substantiallyparallel to a bore axis of the scaffold. The ring struts 230, hingeelements 232, and link struts 234 define a plurality of W-shape closedcells 236. The boundary or perimeter of one W-shape closed cell 236 isdarkened in FIG. 2 for clarity. In FIG. 2, the W-shapes appear rotated90 degrees counterclockwise. Each of the W-shape closed cells 236 isimmediately surrounded by six other W-shape closed cells 236, meaningthat the perimeter of each W-shape closed cell 236 merges with a portionof the perimeter of six other W-shape closed cells 236. Each W-shapeclosed cell 236 abuts or touches six other W-shape closed cells 236.

Referring to FIG. 2, the perimeter of each W-shape closed cell 236includes eight of the ring struts 230, two of the link struts 234, andten of the hinge elements 232. Four of the eight ring struts form aproximal side of the cell perimeter and the other four ring struts forma distal side of the cell perimeter. The opposing ring struts on theproximal and distal sides are parallel or substantially parallel to eachother. Within each of the hinge elements 232 there is an intersectionpoint 238 toward which the ring struts 230 and link struts 234 converge.There is an intersection point 238 adjacent each end of the ring struts230 and link struts 234. Distances 240 between the intersection pointsadjacent the ends of rings struts 230 are the same or substantially thesame for each ring strut 230 in the intermediate portion 216 of thestrut pattern 200. The distances 242 are the same or substantially thesame for each link strut 234 in the intermediate portion 216. The ringstruts 230 have widths 237 that are uniform in dimension along theindividual lengthwise axis 213 of the ring strut. The ring strut widths234 are between 0.15 mm and 0.18 mm, and more narrowly at or about 0.165mm. The link struts 234 have widths 239 that are also uniform indimension along the individual lengthwise axis 213 of the link strut.The link strut widths 239 are between 0.11 mm and 0.14 mm, and morenarrowly at or about 0.127 mm. The ring struts 230 and link struts 234have the same or substantially the same thickness in the radialdirection, which is between 0.10 mm and 0.18 mm, and more narrowly at orabout 0.152 mm.

As shown in FIG. 2, the interior space of each W-shape closed cell 236has an axial dimension 244 parallel to line A-A and a circumferentialdimension 246 parallel to line B-B. The axial dimension 244 is constantor substantially constant with respect to circumferential positionwithin each W-shape closed cell 236 of the intermediate portion 216.That is, axial dimensions 244A adjacent the top and bottom ends of thecells 236 are the same or substantially the same as axial dimensions244B further away from the ends. The axial and circumferentialdimensions 244, 246 are the same among the W-shape closed cells 236 inthe intermediate portion 216.

It will be appreciated from FIG. 2 that the strut pattern for a scaffoldthat comprises linear ring struts 230 and linear link struts 234 formedfrom a radially expanded and axially extended polymer tube. The ringstruts 230 define a plurality of rings 212 capable of moving from anon-deformed configuration to a deformed configuration. Each ring has acenter point, and at least two of the center points define the scaffoldcentral axis. The link struts 234 are oriented parallel or substantiallyparallel to the scaffold central axis. The link struts 234 connect therings 212 together. The link struts 232 and the ring struts 230 definingW-shape closed cells 236. Each W-shaped cell 236 abuts other W-shapedcells. The ring struts 230 and hinge elements 232 on each ring 212define a series of crests and troughs that alternate with each other.Each crest on each ring 212 is connected by one of the link struts 234to another crest on an immediately adjacent ring, thereby forming anoffset “brick” arrangement of the W-shaped cells.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects. Therefore, the appended claims are toencompass within their scope all such changes and modifications as fallwithin the true spirit and scope of this invention.

What is claimed is:
 1. A method for crimping a balloon-expanded stentscaffold to a balloon, comprising the steps of: positioning a scaffoldcomprising a polymer on a support configured for being inserted into acrimping device; deionizing the scaffold while the scaffold ispositioned on the support; inserting the deionized scaffold into thecrimping device while the scaffold is positioned on the support; andreducing the diameter of the deionized scaffold using the crimpingdevice.
 2. A method for crimping a balloon-expanded stent scaffold to aballoon, comprising the steps of: positioning a scaffold comprising apolymer on a support configured for being inserted into a crimpingdevice; deionizing the scaffold; placing the scaffold within thecrimping device; and reducing the diameter of the deionized scaffoldusing the crimping device; wherein after reducing the scaffold diameter,the scaffold is removed from the crimping device then reinserted intothe crimping device and crimped to the balloon; and wherein the scaffoldis formed from a tube comprising PLLA characterized by a glasstransition temperature range having a lower limit of about 55° C., andthe crimping step includes crimping the scaffold to the balloon whilethe scaffold has a temperature of between about 48° C. and 54° C.
 3. Themethod of claim 2, wherein the crimping the scaffold to the balloonincludes a first crimping step, wherein in the first crimping step thescaffold is crimped to a first diameter by placing a crimper head at afirst diameter and holding the crimper head at the first diameter whilethe balloon is inflated to a first pressure.
 4. The method of claim 3,wherein the crimping the scaffold to the balloon includes a secondcrimping step, wherein in the second crimping step the crimper head ismoved to a second diameter, less than the first diameter, and holdingthe crimper head at the second diameter while the balloon is inflated toa second pressure.
 5. The method of claim 4, wherein after the secondcrimping step performing a third crimping step including the crimperhead being moved to a third diameter, less than the second diameter, andholding the crimper head at the third diameter.
 6. A method for crimpinga balloon-expanded stent scaffold to a balloon, comprising the steps of:positioning a scaffold comprising a polymer on a support configured forbeing inserted into a crimping device; deionizing the scaffold; placingthe scaffold within the crimping device; and reducing the diameter ofthe scaffold using the crimping device; wherein after reducing thescaffold diameter, the scaffold is removed from the crimper, reinsertedinto the crimper, then crimped to a balloon; and wherein the scaffold isformed from a tube comprising a polymer characterized by a glasstransition temperature range having a lower limit of Tg-low, and thecrimping to the balloon step includes crimping the scaffold to theballoon while the scaffold has a temperature of between about Tg-low and15 degrees below Tg-low.
 7. The method of claim 6, wherein the polymeris PLLA or PLGA.
 8. The method of claim 6, wherein the temperature rangeis between about Tg-low and 10degrees below Tg-low.
 9. The method ofclaim 8, wherein the temperature range is between about Tg-low and 5degrees below Tg-low.
 10. The method of claim 1, wherein the scaffold isformed from a radially-expanded tube and includes a circumferentialseries of closed cells having a W-shape and linear link strutsconnecting the W-shape cells.
 11. The method of claim 1, wherein thescaffold is deionized while it rests on the support to reduce any staticcharge buildup on the scaffold that might have occurred while thescaffold was positioned on the support.
 12. The method of claim 1,wherein the support is a polymer balloon.
 13. The method of claim 12,wherein the scaffold is made from a radially expanded tube.
 14. Themethod of claim 12, wherein the scaffold polymer is characterized by aglass transition temperature range having a lower limit of Tg-low, andthe crimping to the balloon step includes crimping the scaffold to theballoon while the scaffold has a temperature of between about Tg-low and15 degrees Celsius below Tg-low.
 15. The method of claim 12 wherein thescaffold has a diameter prior to crimping that is at least 2.5 timesgreater than a scaffold diameter after crimping; and wherein the crimpedscaffold and balloon are configured for expanding the scaffold to adiameter that is at least 2.5 times greater than the scaffold diameterafter crimping.
 16. The method of claim 12, wherein the crimping deviceis an iris crimper having jaws configured to plastically deform thescaffold.
 17. The method of claim 1, wherein the scaffold is cut from amaterial comprising a polymer.